Clinical course of early extranodal non-Hodgkin's lymphomas.

The subsequent sites of relapse following local X-ray therapy treatment of early stage non-Hodgkin's lymphoma were analyzed. The short interval to recurrence, the involvement of noncontiguous sites, and the rapid progression to death all suggest that seemingly early extranodal non-Hodgkin's lymphoma often is disseminated at diagnosis and that local treatment alone is ineffective. The analysis of sites of first relapse suggests that extended field treatment such as total nodal irradiation would benefit only a minority of these patients but would be superior to a radiation technique covering only the adjacent lymph node regions. While immediate contiguity of lymph node involvement was often seen with extranodal presentations, the more common pattern of relapse in bone marrow, liver, lung, stomach, and extranodal sites, indicates the need for an effective systemic therapy.     

Epirubicin in non-Hodgkin's lymphomas

Epirubicin (Epi-DX), a new analog of doxorubicin, was administered I.V. once q 3 weeks at the dose of 90 mg/m2 to 20 evaluable patients with non-Hodgkin's lymphomas (NHL). Eighty-two percent of patients with favorable histology and 67% with unfavorable histology achieved complete or partial remissions, with an overall response rate of 75%. Gastrointestinal and hematologic toxicity was generally mild to moderate. Reversible ST-T changes were observed only in two patients. Epi-DX has high activity in patients with NHL, and further studies in combination with other agents are recommended.     

Clinical and biological applications of image analysis in non-Hodgkin's lymphomas

The technical procedures and the main applications of image analysis in non-Hodgkin's lymphoma pathology have been described by reviewing the pertinent literature. With the advent of sophisticated computer-based technology, the possibility of objectively evaluating cell morphology, in situ marker expression, DNA indexes, and complex structural features may become a relevant part of the pathologist's expertise. Copyright © 1998 John Wiley & Sons, Ltd.     

Malignant non-Hodgkin's lymphomas in children

The spectrum of non-Hodgkin's lymphomas (NHL) that occurs in children differs markedly from that in adults. This is probably a consequence of differences in the proportions of precursor and mature lymphoid cells in the immune systems of children and adults, and the greater emphasis on the development of an immunologic repertoire in the child. Childhood NHL can be classified into three main types based on histology, all of them diffuse: lymphoblastic, small noncleaved cell, and large cell. The majority of lymphoblastic lymphomas are of immature T cell (thymocyte) origin, although a few have a B cell precursor phenotype. All express the enzyme terminal transferase. Small noncleaved lymphomas express B cell characteristics, as do the majority do the majority of large cell lymphomas, although a small proportion of the latter express T cell characteristics. Very few are of true histiocytic origin. Little is known of the epidemiology of lymphoblastic and large cell lymphomas. However, using histology as a diagnostic criterion, both occur throughout the world and occur primarily, as do all childhood NHL, in the first two decades of life. There appear to be at least two types of small noncleaved cell lymphomas, both of which are associated with specific chromosomal translocations. An endemic form occurs at high frequency in equatorial Africa, and a sporadic form occurs at low frequency throughout the world. The endemic tumor is associated with the Epstein-Barr virus, it has a high incidence of jaw tumors, and has a breakpoint on chromosome 8 that is usually some distance upstream of the c-myc oncogene. The sporadic tumor is only occasionally associated with EBV, it often involves the bone marrow, particularly at relapse, and has a breakpoint on chromosome 8 that is usually very close to or within the c-myc oncogene. Childhood NHL is rarely truly localized, and treatment regimens are always based on chemotherapy. There is no evidence that radiation is beneficial when modern combination drug regimens are employed as the primary therapeutic modality. Prophylactic treatment to the central nervous system is recommended in nearly all patients, and intrathecal drugs, usually supplemented by some form of high-dose or intermediate-dose methotrexate, appear to represent adequate prophylaxis to the CNS. The most effective regimens result in cure in almost all patients who have limited overt disease, and in a high proportion (50 to 75 per cent) of patients with extensive disease, although patients with bone marrow involvement do poorly with most regimens.(ABSTRACT TRUNCATED AT 400 WORDS)     

DNA rearrangements in non-Hodgkin's lymphomas

The configuration of DNA at genetic loci that undergo somatic recombination in lymphocytes provides genetic markers that are useful in the diagnosis and characterization of non-Hodgkin's lymphomas. The loci containing rearranged DNA fall into three groups: the immunoglobulin genes, the T cell receptor genes and sites of chromosomal rearrangements, such as chromosomal translocations. DNA fragments cloned from these loci can be used as hybridization probes to characterize the rearranged DNA sequences in biopsy tissues. Only probes for chromosomal rearrangements are capable of directly diagnosing neoplasia and histological subtypes; however, probes for rearrangements of immunoglobulin and T cell receptor genes are valuable for detecting clonal proliferations, determining B or T cell derivation of tumours and distinguishing individual clones of lymphocytes from each other. Applications of DNA rearrangements have already yielded a number of important findings concerning the biology of human lymphoma. These discoveries have included the existence of multiclonal B cell cancers, the widespread dissemination of occult tumour to lymph nodes in mycosis fungoides, the high incidence of circulating tumour cells in patients with low grade lymphomas and the molecular heterogeneity of chromosomal break-points in follicular lymphomas.     

Monoclonal gammopathies in B-cell non-Hodgkin's lymphomas

The association of monoclonal gammopathy (MG) with B-cell non-Hodgkin's lymphomas (NHL) is a well known phenomenon. The aim of the present work was to study the incidence, type of monoclonal component and prognostic significance of MG in a population of 255 cases with B-cell NHL. Among 255 evaluable patients with B-cell NHL, 145 were males and 110 females with a median age of 58 years (range 18-85). There were 166 patients with the various subtypes of aggressive (intermediate/high grade) NHL and 89 with the various subtypes of low risk. MG was detected in 44 patients (17.2%) with a median age of 61 years (range 23-79). There were 22 cases (8.6%) with IgG type (IgG/(k) 15, IgG/(lambda) 7), 4 cases (1.6%) with (IgA/(k) 3, IgA/(lambda) 1) and 18 cases (7.0%) with IgM (IgM/(k) 12 IgM/(lambda) 6). MG was found in 15.6% of the patients with aggressive NHL, while in low risk NHL the incidence was 20.2% (N.S.). The type of MG according to histological classification was as follows: Aggressive NHL: IgG 17 cases, IgA 2 cases, IgM 7 cases: low risk NHL: IgG 5 cases, IgA 2 cases, IgM 11 cases. The distribution of MG according to stage of the disease was as follows: stage I (4.5%), stage II (18%), stage III (6.8%) and stage IV (70.4%). The median survival of patients with aggressive NHL with MG was 17 months compared to 40 months of those without (P=0.22). Similarly the median survival of patients with low risk NHL and MG was 51.5 months compared to 38.5 months of those without (P=0.90). In conclusion MG was detected in 17.2% of cases with B-cell NHL. IgG-MG was more frequent in cases with aggressive NHL, while IgM in cases with low risk NHL. MG was mostly associated with advanced stage and had not any prognostic significance on survival.     

Histologic conversion in the non-Hodgkin's lymphomas

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.     

Cyclooxygenase-2 expression in non-Hodgkin's lymphomas

Cyclooxygenase 2 (Cox-2) is a key enzyme in prostaglandin synthesis and it has an important role in the pathogenesis of various malignancies. Cox-2 has been studied in solid tumors; however, studies about the role of Cox-2 in non-Hodgkin's lymphomas (NHL) are limited. The aim of this study is to determine the importance of Cox-2 expression in lymphomas. To this end, Cox-2 expression was determined in 177 cases with NHL. In histological terms, 60 cases (33%) had low grade and 117 (67%) had aggressive lymphoma. Ninety-nine cases were found to be positive for Cox-2 (56%); Cox-2 score was between 50 and 100, 101 and 200 and over 200 in 38, 46 and 15 cases, respectively. There was an important association between aggressive histology and Cox-2 expression: Cox-2 was negative in about half of the cases with indolent morphology, while two thirds of the Cox-2 positive cases had aggressive histology (p = 0.036).There was no significant association between Cox-2 expression and clinical-laboratory parameters. Although the overall survival times were longer in cases with lower or no Cox-2 expression as compared with higher Cox-2 expression, the difference was not significant. In conclusion Cox-2 expression is seen about 60% of the cases with NHL and is associated with aggressive morphology.     

Lymphocyte markers in non-Hodgkin's lymphomas.

The lymphocyte marker pattern of non-Hodgkin's lymphoma cells was related to current concepts of lymphoma classification. In a series of 28 lymphomas lymphocyte markers indicated that 2 were of histiocytic origin, 2 were unclassifiable, none were derived from T cells and the remainder were B-cell neoplasms. The immunoglobulin heavy chain associated with the B-cell tumours was gamma in one case, alpha in one case but was mu in the majority of cases, reflecting the predominance of this heavy chain, together with delta chains, on normal lymph node lymphocytes in man. delta chains accompanied mu chains on the tumour cells in 6/17 lymphomas in which anti-delta staining was performed. delta chains were not found on any lymphomas other than well differentiated diffuse lymphocytic types. There was evidence of a reduction in surface immunoglobulin, Fcgamma and C3 receptors on undifferentiated lymphoma cells. T lymphocytes of normal morphology were present in all lymphomas except one, and were more numerous in follicular lymphomas than in diffuse tumours.     

Trends in mortality from non-Hodgkin's lymphomas

Trends in death certification rates from non-Hodgkin's lymphomas (NHL) were analyzed on the basis of the World Health Organization database over the period 1969-1998. Until the late 1970s, mortality from NHL was similar in the European Union (EU), the USA and Japan, i.e. around 3/100,000 males and 2/100,000 females. Over the last two decades, NHL mortality in the EU rose to 4.4/100,000 males and 2.8/100,000 females. Upward trends were greater in the USA, whose rates approached 6/100,000 males and 4/100,000 females in the late 1990s, and were observed in Japan, too.     

New biologic markers in non-Hodgkin's lymphomas

Many of the tumor markers mentioned in this article may seem to be of only research or theoretic interest. However, many of those mentioned are likely to be of great clinical utility in the future. In particular, the strength of these immunohistochemical findings have been compared with standard clinical prognostic features (e.g., stage, age, B symptoms) and have been modeled to show independent prognostic relevance in both intermediate-grade and low-grade lymphomas. Beyond their predictive value, these markers have identified phenotypes that may serve as new therapeutic targets: (1) restoration of HLA loss with alpha and gamma interferons; and (2) restoration of tumor-infiltrating T-cell lymphocytes with interleukin-2. New phenotype-directed cytokine therapies seem compelling with this new knowledge. We await future prospective trials of phenotyping to further refine this new exciting prospect.     

Treatment of non-Hodgkin's lymphomas in elderly patients

The roles of evolving treatment strategies for non-Hodgkin's lymphomas (NHL) in elderly patients are still not well defined and their effects on the overall epidemiology of the disease are still not clear. Three questions arise when discussing the management of NHL in elderly patients. First, should older patients be treated with the same regimens usually administered to younger patients? Second, are health outcomes of elderly patients similar to those usually observed in young patients, particularly response rate and overall survival? Third, which strategies should be adopted to improve overall health outcomes? Periodic review of the literature and updated data on the management of NHL in elderly patients may provide an answer to all these queries. In essence, older patients must be treated with the same intensive approaches that are usually reserved for younger patients. The results reported in randomized controlled clinical trials are consistent with the capability of older patients to exhibit overall response rate, event-free survival, and overall survival similar to those observed in their younger counterparts. Combining chemotherapy and monoclonal antibodies seems to be the main optional strategy for better outcomes in elderly patients. In contrast, knowledge concerning the management of indolent lymphomas in elderly patients is still lacking, and available clinical data are limited in this setting, especially in patients with poor prognostic factors who may need an immediate therapeutic intervention.     

Phenotypic expression of non-Hodgkin's lymphomas in China

Monoclonal antibodies were used to label malignant lymphomas obtained from 57 patients. On the basis of morphologic criteria, 18 lymphomas were the B-cell type, 10 were the T-cell type, and 6 were histiocytic; for 23 the type could not be determined. After monoclonal antibody labeling, 18 lymphomas of B-cell lineage were confirmed, 16 of the T-cell type were demonstrated, 6 were true histiocytic, and 17 were the null cell (non-T, non-B) type. Of the 16 lymphomas of T-cell lineage, 6 were lymphoblastic and 10 were the peripheral type. The percentages of cell types in the non-Hodgkin's lymphomas were as follows: B-cell, 31.5%; T-cell, 28%; null cell, 29%; and histiocytic, 10%. Of the 16 lymphomas of T-cell origin, 15 belonged to helper T-cell subsets (Leu1+, Leu4+, and Leu3a+), and the la marker was positive in all 16. Of the 18 B-cell lymphomas, 14 were kappa-positive and 4 were lambda-positive. Eleven were both B1- and kappa-positive, and 1 was kappa-positive but B1-negative. In the 4 cases that were lambda-positive, 2 were both lambda- and B1-positive. The results indicate that Leu4, Leu2a, Leu3a, and B1 are the most important markers to differentiate T-cell and B-cell lymphomas for pathologic classification. The findings also show a higher percentage of T-cell neoplasm in China as compared to that in Western countries.     

Immunophenotypic characterization of follicle-center-cell-derived non-Hodgkin's lymphomas

The distribution of the BLA, CALLA (CD 10), AC-2 (CD 39), MHM-6 (CD 23), LB-I, and 351C5 (CD 45R) antigens in 40 non-Hodgkin's lymphomas was demonstrated by immunohistochemical staining of frozen tissue sections. Nine out of 10 centroblastic and centrocytic follicular and diffuse type of lymphomas (CB/CC F/D) and all 10 cases of CB/CC follicular lymphomas were BLA+ and CALLA+. A few cases also showed weak expression of activation antigens (AC-2, MHM-6 and LB-I) and 351C5. In contrast, 3 CC and 3 lymphoblastic (non-Burkitt) lymphomas showed a heterogeneous pattern of distribution with dominating activation antigen expression. A single case of lymphoblastic lymphoma of Burkitt-like type expressed BLA and CALLA but not activation antigens. In reactive follicular center and FCC lymphomas different cell populations appeared to express BLA and activation antigens, respectively. Assessment of staining intensity and proportion of the stained cells indicated that almost all BLA+ cells are CALLA+. CALLA+ BLA- cells were regularly present, in addition. The co-expression of BLA and CALLA in the same cell was confirmed by double immuno-enzymatic staining. By the same technique, BLA+ and CALLA+ cells were shown to be activation-antigen negative.